The University of Louisville proposes to establish a Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPMBEID). Our long-term objective is to support the development of gene-based countermeasures and diagnostic approaches based on system changes that occur during host- pathogen interactions. Focusing on host-based biothreat and emerging infectious disease research should allow the development of broad-spectrum interventions to infectious agents rather than the current paradigm of "one bug/one vaccine" approach so prevalent today. Our specific aims are to 1) meet the expanding needs of current researchers who work with Category A, B, or C priority pathogens at the University of Louisville; 2) expand facilities so that we can add an additional six faculty investigators who work with these agents; 3) assemble a unique mix of technologies in a free standing BSL3 facility so that the instrumentation and expertise is available on site to manipulate experimental materials and avoid the need for shipping material off site; and 4) to serve as a resource for investigators from other institutions in our region who can benefit from the unique mix of technologies we will assemble in the facility as well as be prepared to bring those technologies to bear in the event of a bioterrorism emergency. The University created a superb team of investigators and administrators to shepherd this project from application to operation. We are committed to working with NIAID and believe our missions can be mutually reinforced by building a RBL in Louisville. Principal Investigator: Martin, Nancy C. 5. Budget (Supporting Documents) 5.a. Source of Nonfederal Funding: The University of Louisville proposes to establish a stand alone RBL facility called the Center of Predictive Medicine for Biothreat and Emerging Infectious Disease. This facility will be strategically located on the 180-plus acre Shelby campus, the location of a Science and Technology park with a developing emphasis on Homeland Security related activities. The building itself will be a single-story building of brick CMU construction. The facility building will include a penthouse that will be limited to facility mechanical and heating, ventilation, and air-conditioning (HVAC) components. The +/- 4 acre site is topographically located atop a bluff that is surrounded by steep gradients to the north, west, and south and is further protected from surrounding development due to the presence of a regional storm water detention basin. Further details regarding the site and its location are provided in Section 7a. of this application. The rationale for the proposed center is based on unmet needs of current and future researchersat Uof L who focus on biothreat and emerging infectious diseases at U of L and will also serve other universities in the region through the Ohio Valley Affiliates for Life Sciences (OVALS), an organization dedicated to leveraging resources at member institutions for the benefit of all members. In planning the project, we considered three aspects in detail: 1. the construction costs necessary to build a stand-alone 30,000 square foot facility; 2. the architectural requirements to satisfy threat-risk evaluations; and 3. the specific needs of electric, ventilation, and other structural support for housing heavy research equipment such as mass spectroscopic instruments for proteomic studies, Fluorescence Activated Cell Sorters, etc as well as computer server equipment for datamining the voluminous data that will be generated. Thus, the final budget will support the construction and equipping of a facility that will meet the overall goal of developing gene-based countermeasures and diagnostic approaches based on system changes that occur during host- pathogen interactions. The architectural and operations plan envisions a shared lab approach to maximize the use of the proposed unique state-of-the art biomedical research capability by U of L and OVAL scientists as well as their colleagues from elsewhere in the nation. With full institutional support, the current budget is based on the continuous interaction and discussions of a working team composed of users, i.e. the researchers and administrators responsible for animal care, biosafety, and construction and an outside construction consulting firm, CUH2A as well as an outside threat-risk consultant, Tetra Tech, Inc. The final budget for the entire proposed facility is $34,629,950.00 with the total Non-Allowable Costs of $5,369,700 and the total Allowable Costs of $29,260,250. In this proposal, we are seeking funding for 75% of the total Allowable-Costs for a total of $21,945,187.00. The University will cost share $7,315,063 in Allowable-Costs. This amount plus the Non- Allowable Costs total $12,684,763; the plan for the source of this non-federal funding is: i. Commitment of $3 million in cash from the funds available in the offices of Vice President for Health Affairs and Senior Vice President for Research; $1.5 million respectively. ii. Commitment of $12,684,763 to be covered by bonding. This funding commitment is described in a letter from the President of the University of Louisville, Dr. James Ramsey to the Principal Investigator, Dr. Nancy Martin (see next page). 5.b. Composition of Funds: Federal Funding: $21,945,187,50; Non-Federal Funding: $12,684,763: Allowable: $7,315,063; Non-Allowable:$5,369.700. i. Cash: $3,000,000 ii. Bond: $9,684,763 (An additional $3,000,000 Contingency Fund will also be generated by bonding.)